Chronic obstructive pulmonary disease is a leading cause of death and disability in the U.S. Factors, which have impaired effective research in COPD, include misconceptions that the disease is irreversible and untreatable and a lack of consensus on optimal functional outcome measures available to assess this patient population. The COPD clinical research network (CRN) represents an important commitment by the NIH to address these impediments to effective research in COPD. Thus our primary aim of this proposal will be to: CONTRIBUTE PRODUCTIVELY TO THE COPD CLINICAL RESEARCH NETWORK BY MEETING NECESSARY SUBJECT RECRUITMENT GOALS, PROVIDING EXPERT LOCAL EXECUTION OFA MULTI-CENTER TRIAL AND OFFER EXPERTISE IN INNOVATIVE TECHNIQUES IN SUBJECT CHARACTERIZATION AND OUTCOMES. Our center brings extensive experience gained in multicenter clinical trials including the NIH sponsored NETT, FORTE and Lung Health Studies. This experience combined with our access to large numbers of research-interested subjects confirms that we would be a strong contributor to the COPD-CRN. The breadth of our recruitment extends from our IRB approved emphysema registry; subjects recently completing the Lung Health study; our participation with the Pittsburgh SPORE (high risk smoker screening project); and an extended tertiary care hospital network. We also bring a strong record of scientific investigation in the use of exercise, pulmonary mechanics and quantitative computed tomography in the assessment of outcome in COPD. These skills synergize with those of our strong basic science collaborators at the University of British Columbia and in our own Division of Clinical Pharmacology. A recent journal editorial noted: "the combination of a well characterized patient population in Pittsburgh with the pathology expertise in Vancouver, demonstrates the power of collaboration between centers geographically separated." Our proposed projects represent clinical trials targeting different categories of outcome in COPD that have integrity, independent of the specific intervention. Project 1 addresses the impact of an anti-inflammatory agent (fluticasone) on the severity of COPD exacerbation. We would consider this design as a basis for testing other evolving classes of anti-inflammatory pharmaceutical agents. Project 2 addresses the individual variation in response to inhaled bronchodilators and attempts to discriminate subjects, which are most likely to benefit, based upon innovative measures of lung function, functional performance and symptoms. Such an approach can be applied to other interventions hypothesized to improve functional capacity. We believe that our strong clinical trials experience, extraordinary access to research interested subjects and basic and clinical science record would make us strong participants in the COPD-CRN.